tbuckley/cabot-search huggingface dataset:
Triple-functional bone adhesive with enhanced internal fixation, bacteriostasis and osteoinductive properties for open fracture repair
Authors: Yusheng Yang, Shenghui Su, Shencai Liu, Weilu Liu, Qinfeng Yang, Liangjie Tian, Zilin Tan, Lei Fan, Bin Yu, Jian Wang, Yanjun Hu
Journal: Bioactive Materials (2023)

At present, effective fixation and anti-infection implant materials represent the mainstay for the treatment of open fractures. However, external fixation can cause nail tract infections and is ineffective for fixing small fracture fragments. Moreover, closed reduction and internal fixation during the early stage of injury can lead to potential bone infection, conducive to bone nonunion and delayed healing. Herein, we designed a bone adhesive with anti-infection, osteogenic and bone adhesion fixation properties to promote reduction and fixation of open fractures and subsequent soft tissue repair. It was prepared by the reaction of gelatin (Gel) and oxidized starch (OS) with vancomycin (VAN)-loaded mesoporous bioactive glass nanoparticles (MBGNs) covalently cross-linked with Schiff bases. Characterization and adhesion experiments were conducted to validate the successful preparation of the Gel-OS/VAN@MBGNs (GOVM-gel) adhesive. Meanwhile, in vitro cell experiments demonstrated its good antibacterial effects with the ability to stimulate bone marrow mesenchymal stem cell (BMSCs) proliferation, upregulate the expression of alkaline phosphatase (ALP) and osteogenic proteins (RunX2 and OPN) and enhance the deposition of calcium nodules. Additionally, we established a rat skull fracture model and a subcutaneous infection model. The histological analysis showed that bone adhesive enhanced osteogenesis, and in vivo experiments demonstrated that the number of inflammatory cells and bacteria was significantly reduced. Overall, the adhesive could promote early reduction of fractures and antibacterial and osteogenic effects, providing the foothold for treatment of this patient population.
Reply: Mesenchymal stromal (stem) cell therapy modulates miR-193b-5p expression to attenuate sepsis-induced acute lung injury
Authors: Claudia C. dos Santos, Chirag M. Vaswani, Shirley H.J. Mei, Patricia R.M. Rocco, Daniel J. Weiss, Duncan J. Stewart, W. Conrad Liles
Journal: European Respiratory Journal (2023)

<b>The therapeutic effect of mesenchymal stromal cells (MSCs) is in part due to regulation of host-derived epigenetic modulators – microRNAs – which in turn regulate the transcriptional response to inflammation and injury in a pre-clinical model of ALI</b> https://bit.ly/3jMzCw2
Cellular heterogeneity insights and molecular signatures in paediatric sleep apnoea
Authors: Manuel Sánchez-de-la-Torre, Ferran Barbé
Journal: European Respiratory Journal (2023)

Obstructive sleep apnoea (OSA) in children, with a prevalence of 1–5.7% [1], is one of the most common causes of sleep disordered breathing in children, with a peak of occurrence at 2–8 years old [2]. Paediatric sleep apnoea is typically associated with snoring, indicating the presence of increased upper airway resistance. The most common factor underlying the presence of paediatric sleep apnoea is hypertrophy of the upper airway lymphadenoid tissues, which results in increased upper airway collapsibility. Moreover, obesity, neurological or neuromuscular diseases, and gastro-oesophageal reflux are some risk factors that frequently occur in paediatric sleep apnoea. Single-cell sequencing emerges as a platform to observe and characterise relevant morbidity-related pathophysiologic mechanisms associated with paediatric OSA <https://bit.ly/3jroqVo>
Inhaled therapy, cardiovascular risk and benefit–risk considerations in COPD: innocent until proven guilty, or<i>vice versa</i>?
Authors: Lucile Regard, Pierre-Régis Burgel, Nicolas Roche
Journal: European Respiratory Journal (2023)

<b>Relationships between inhaled therapy, cardiovascular risk and prognosis in patients with COPD are complex. Globally, the benefit–risk ratio of inhaled bronchodilators and corticosteroids appears largely favourable. Studies in subgroups at risk are needed.</b>https://bit.ly/3VS41Hq
“Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus-induced expansion of inflammatory macrophages.” K. Hönzke, B. Obermayer, C. Mache,<i>et al</i>.<i>Eur Respir J</i>2022; 60: 2102725
Journal: European Respiratory Journal (2023)
Sympathetic activation in patients with heart failure and central sleep apnoea: is it friend or foe?
Authors: Maria R. Bonsignore, Maria Teresa La Rovere
Journal: European Respiratory Journal (2023)

<b>This sub-study of the SERVE-HF study found unchanged peripheral nervous sympathetic activity (MSNA) in heart failure patients on medical treatment or on ASV after 12 weeks. Reduced MSNA was associated with worse prognosis only in the ASV group.</b>http://bit.ly/3i5WRRb
Targeting galectin-driven regulatory circuits in cancer and fibrosis
Authors: Karina V. Mariño, Alejandro J. Cagnoni, Diego O. Croci, Gabriel A. Rabinovich
Journal: Nature Reviews Drug Discovery (2023)

Galectins are a family of endogenous glycan-binding proteins that have crucial roles in a broad range of physiological and pathological processes. As a group, these proteins use both extracellular and intracellular mechanisms as well as glycan-dependent and independent pathways to reprogramme the fate and function of numerous cell types. Given their multifunctional roles in both tissue fibrosis and cancer, galectins have been identified as potential therapeutic targets for these disorders. Here, we focus on the therapeutic relevance of galectins, particularly galectin 1 (GAL1), GAL3 and GAL9 to tumour progression and fibrotic diseases. We consider an array of galectin-targeted strategies, including small-molecule carbohydrate inhibitors, natural polysaccharides and their derivatives, peptides, peptidomimetics and biological agents (notably, neutralizing monoclonal antibodies and truncated galectins) and discuss their mechanisms of action, selectivity and therapeutic potential in preclinical models of fibrosis and cancer. We also review the results of clinical trials that aim to evaluate the efficacy of galectin inhibitors in patients with idiopathic pulmonary fibrosis, nonalcoholic steatohepatitis and cancer. The rapid pace of glycobiology research, combined with the acute need for drugs to alleviate fibrotic inflammation and overcome resistance to anticancer therapies, will accelerate the translation of anti-galectin therapeutics into clinical practice. Galectins are glycan-binding proteins with broad roles in physiological and pathological processes. Here, Rabinovich and colleagues discuss the therapeutic relevance of galectins to cancer and fibrosis and review the various strategies to target galectins and their progress in clinical trials.
PDPN positive CAFs contribute to HER2 positive breast cancer resistance to trastuzumab by inhibiting antibody-dependent NK cell-mediated cytotoxicity
Authors: Ruoxin Du, Xiangmei Zhang, Xiyan Lu, Xiangmin Ma, Xinyan Guo, Chao Shi, Xiaofei Ren, Xindi Ma, Yutong He, Yuan Gao, Yunjiang Liu
Journal: Drug Resistance Updates (2023)
Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial
Authors: Binghe Xu, Qingyuan Zhang, Xichun Hu, Qing Li, Tao Sun, Wei Li, Quchang Ouyang, Jingfen Wang, Zhongsheng Tong, Min Yan, Huiping Li, Xiaohua Zeng, Changping Shan, Xian Wang, Xi Yan, Jian Zhang, Yue Zhang, Jiani Wang, Liang Zhang, Ying Lin, Jifeng Feng, Qianjun Chen, Jian Huang, Lu Zhang, Lisong Yang, Ying Tian, Hongyan Shang
Journal: Acta Pharmaceutica Sinica B (2023)

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).
The oropharynx of men using HIV pre-exposure prophylaxis is enriched with antibiotic resistance genes: A cross-sectional observational metagenomic study
Authors: Christophe Van Dijck, Jolein Gyonne Elise Laumen, Tessa de Block, Saïd Abdellati, Irith De Baetselier, Achilleas Tsoumanis, Surbhi Malhotra-Kumar, Sheeba Santhini Manoharan-Basil, Chris Kenyon, Basil Britto Xavier
Journal: Journal of Infection (2023)
Endocrine modulation of brain-skeleton axis driven by neural stem cell-derived perilipin 5 in the lipid metabolism homeostasis for bone regeneration
Authors: Lingchi Kong, Haoyu Zhao, Feng Wang, Rui Zhang, Xiangyun Yao, Rongtai Zuo, Juehong Li, Jia Xu, Yun Qian, Qinglin Kang, Cunyi Fan
Journal: Molecular Therapy (2023)

Factors released from the nervous system always play crucial roles in modulating bone metabolism and regeneration. How the brain-driven endocrine axes maintain bone homeostasis, especially under metabolic disorders, remains obscure. Here, we found that neural stem cells (NSCs) residing in the subventricular zone participated in lipid metabolism homeostasis of regenerative bone through exosomal perilipin 5 (PLIN5). Fluorescence-labeled exosomes tracing and histological detection identified that NSC-derived exosomes (NSC-Exo) could travel from the lateral ventricle into bone injury sites. Homocysteine (Hcy) led to osteogenic and angiogenic impairment, whereas the NSC-Exo were confirmed to restore it. Mecobalamin, a clinically used neurotrophic drug, further enhanced the protective effects of NSC-Exo through increased PLIN5 expression. Mechanistically, NSC-derived PLIN5 reversed excessive Hcy-induced lipid metabolic imbalance and aberrant lipid droplet accumulation through lipophagy-dependent intracellular lipolysis. Intracerebroventricular administration of mecobalamin and/or AAV-shPlin5 confirmed the effects of PLIN5-driven endocrine modulations on new bone formation and vascular reconstruction in hyperhomocysteinemic and high-fat diet models. This study uncovered a novel brain-skeleton axis that NSCs in the mammalian brain modulated bone regeneration through PLIN5-driven lipid metabolism modulation, providing evidence for lipid- or bone-targeted medicine development.
Stable HIV decoy receptor expression after in vivo HSC transduction in mice and NHPs: Safety and efficacy in protection from SHIV
Authors: Chang Li, Anna Kate Anderson, Hongjie Wang, Sucheol Gil, Jiho Kim, Lishan Huang, Audrey Germond, Audrey Baldessari, Veronica Nelson, Katharine J. Bar, Christopher W. Peterson, John Bui, Hans-Peter Kiem, André Lieber
Journal: Molecular Therapy (2023)

We aim to develop an in vivo hematopoietic stem cell (HSC) gene therapy approach for persistent control/protection of HIV-1 infection based on the stable expression of a secreted decoy protein for HIV receptors CD4 and CCR5 (eCD4-Ig) from blood cells. HSCs in mice and a rhesus macaque were mobilized from the bone marrow and transduced by an intravenous injection of HSC-tropic, integrating HDAd5/35++ vectors expressing rhesus eCD4-Ig. In vivo HSC transduction/selection resulted in stable serum eCD4-Ig levels of ∼100 μg/mL (mice) and >20 μg/mL (rhesus) with half maximal inhibitory concentrations (IC
Orchestrating antigen delivery and presentation efficiency in lymph node by nanoparticle shape for immune response
Authors: Hongjuan Zhao, Yatong Li, Beibei Zhao, Cuixia Zheng, Mengya Niu, Qingling Song, Xinxin Liu, Qianhua Feng, Zhenzhong Zhang, Lei Wang
Journal: Acta Pharmaceutica Sinica B (2023)

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4+ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8+ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.
The value of large-scale studies of sleep and cognition
Authors: Michael W.L. Chee, Adrian R. Willoughby
Journal: Trends in Neurosciences (2023)

Large-scale, global studies providing representative characterisation of sleep and its relation to cognitive performance are rare. In a recent study using a video game to assess spatial navigation, Coutrot and colleagues found that, among participants aged 54-70 years, optimal wayfinding performance was associated with a self-reported sleep duration of 7 h. The results also showed that, while the effects of age and gender on sleep duration were consistent across countries, geography and/or culture significantly modulated sleep duration, a finding that merits further study.
The Chemotherapy of Gestational Trophoblastic Disease
Authors: Donald P. Goldstein
Journal: JAMA (1972)

During the five years from July 1, 1965, through June 30, 1970, a total of 247 patients with molar pregnancy and gestational trophoblastic disease were treated at the New England Trophoblastic Disease Center, Boston. Of this number, 160 were treated, for uncomplicated molar pregnancy and 87 for trophoblastic disease. A new therapeutic classification based on histology, duration of disease, initial gonadotropin level prior to commencement of therapy, extent and nature of metastases, and outcome is proposed to guide the clinician in diagnosis and management.
Recovery from Rabies
Authors: Alan C. Jackson
Journal: New England Journal of Medicine (2005)

Worldwide, some 55,000 people die every year from rabies, mostly in Asian and African countries where canine rabies is endemic. Children are frequently the victims of rabies. In the United States, indigenous cases of rabies in humans usually occur through transmission of rabies virus from wildlife vectors, and molecular characterization of the variants indicates that the majority of these cases originate from insect-eating bats.In this issue of the Journal, Willoughby et al.1 report the case of a young patient in whom rabies developed after a clear history of having been bitten by a bat. Most of the cases of . . .
Failure of Renal Transplantation in Primary Oxalosisn
Authors: Johannes Klauwers
Journal: JAMA (1969)

Severe renal insufficiency developed in a young man ill for many years with primary oxalosis. We felt that a renal transplant might reverse the enzymatic deficiency of glyoxylate transamination and prevent the deposition of oxalate crystals in the kidney. However, the transplant did not help, and the patient died with evidence of deposits of oxalate in the transplanted kidney and throughout his tissues. We believe that transplants should not be performed in primary oxalosis, but methods should be developed where glyoxylate would be converted to glycine instead of insoluble oxalate. <h3>Report of a Case.—</h3> A 22-year-old white man entered the Stanford University Medical Center because of renal failure and for a possible kidney transplant. When the patient was 3 years old, oxalate nephrolithiasis developed with removal of a right ureteral calculus. Since then, many renal calculi and pyelonephritis developed. In October 1967, he experienced extreme weakness and dyspnea, had a
A national programme to scale-up decentralised hepatitis C point-of-care testing and treatment in Australia
Authors: Jason Grebely, Corey Markus, Louise M Causer, David Silk, Simon Comben, Andrew R Lloyd, Maria Martinez, Evan B Cunningham, Mim O'Flynn, Gregory J Dore, Susan Matthews, Samira Hosseini-Hooshyar, Yumi Sheehan, Ineke Shaw, Philip Cunningham, Carrie Fowlie, Alison D Marshall, Marianne Byrne, Carla Treloar, Sophy TF Shih, Richard T Gray, Virginia Wiseman, Tanya L Applegate, Rebecca Guy, Marianne Martinello, Behzad Hajarizadeh, Lise Lafferty, Wayne Dimech, Liza Cabuang, Olivia Dawson, Philip Read, Alisa Pedrana, Alexander J Thompson, Joss O'Loan
Journal: The Lancet. Gastroenterology & hepatology (2023)
A “built-up” composite film with synergistic functionalities on Mg–2Zn–1Mn bioresorbable stents improves corrosion control effects and biocompatibility
Authors: Zhenglong Dou, Shuiling Chen, Jiacheng Wang, Li Xia, Manfred F. Maitz, Qiufen Tu, Wentai Zhang, Zhilu Yang, Nan Huang
Journal: Bioactive Materials (2023)

Control of premature corrosion of magnesium (Mg) alloy bioresorbable stents (BRS) is frequently achieved by the addition of rare earth elements. However, limited long-term experience with these elements causes concerns for clinical application and alternative methods of corrosion control are sought after. Herein, we report a "built-up" composite film consisting of a bottom layer of MgF2 conversion coating, a sandwich layer of a poly (1, 3-trimethylene carbonate) (PTMC) and 3-aminopropyl triethoxysilane (APTES) co-spray coating (PA) and on top a layer of poly (lactic-co-glycolic acid) (PLGA) ultrasonic spray coating to decorate the rare earth element-free Mg-2Zn-1Mn (ZM21) BRS for tailoring both corrosion resistance and biological functions. The developed "built-up" composite film shows synergistic functionalities, allowing the compression and expansion of the coated ZM21 BRS on an angioplasty balloon without cracking or peeling. Of special importance is that the synergistic corrosion control effects of the "built-up" composite film allow for maintaining the mechanical integrity of stents for up to 3 months, where complete biodegradation and no foreign matter residue were observed about half a year after implantation in rabbit iliac arteries. Moreover, the functionalized ZM21 BRS accomplished re-endothelialization within one month.
Clinical factors associated with skin neoplasms in individuals with Lynch syndrome in a longitudinal observational cohort
Authors: Connie S. Zhong, Miki Horiguchi, Hajime Uno, Chinedu Ukaegbu, Anu Chittenden, Nicole R. LeBoeuf, Sapna Syngal, Vinod E. Nambudiri, Matthew B. Yurgelun
Journal: Journal of the American Academy of Dermatology (2023)
Neoadjuvant sintilimab and chemotherapy in patients with potentially resectable esophageal squamous cell carcinoma (KEEP-G 03): an open-label, single-arm, phase 2 trial
Authors: Xiaofeng Chen, Xiang Xu, Danping Wang, Jinyuan Liu, Jing Sun, Mingjie Lu, Rui Wang, Bingqing Hui, Xiaofei Li, Chenchen Zhou, Min Wang, Tianzhu Qiu, Shiyun Cui, Nana Sun, Yang Li, Fufeng Wang, Cuicui Liu, Yang Shao, Jinhua Luo, Yanhong Gu
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background The standard neoadjuvant treatments in patients with esophageal squamous cell carcinoma (ESCC) still have either poor safety or efficacy. Better therapies are needed in China. Methods This was an open-label, single-arm, phase 2 trial. Patients with potentially resectable ESCC (cT1b-3, Nany, M0 or T4a, N0-1, or M0) received preoperative intravenous sintilimab plus triplet chemotherapy (liposomal paclitaxel, cisplatin, and S-1) every 3 weeks for two cycles. The primary endpoints were safety and surgical feasibility; the secondary endpoint was major pathological response (MPR) rate. Genomic biomarkers (genetic mutations, tumor mutational burden (TMB), circulating tumor DNA status and immune microenvironment) in baseline tumor samples were investigated. Results All 30 patients completed two cycles of neoadjuvant treatment and underwent surgical resection. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 36.7% (11/30) of patients. The most frequent TRAEs were decreased white cell count (76.7%), anemia (76.7%), and decreased neutrophil count (73.3%). All TRAEs were hematological toxicities; none caused ≥30 days surgical delay. The MPR and pathological complete response (pCR) rates were 50.0% (15/30; 95% CI 33.2 to 66.9) and 20.0% (6/30; 95% CI 9.5 to 37.3), respectively. Patients with higher TMB and more clonal mutations were more likely to respond. ERBB2 alterations and ctDNA high-releaser status have a negative correlation with neoadjuvant ICI response. No significant difference was observed between therapeutic response and tumor immune microenvironment. Conclusions Neoadjuvant sintilimab plus platinum-based triplet chemotherapy appeared safe and feasible, did not delay surgery and induced a pCR rate of 20.0% in patients with potentially resectable ESCC. Trial registration number NCT03946969 .
Issue Information ‐ General Info
Journal: Arthritis & Rheumatology (2023)

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